DESCRIPTION: (Applicant's Abstract) This proposal is aimed at understanding the mechanisms by which visual information gains access to visual cortical networks and is processed during different operational modes of the lateral geniculate nucleus. The individual neurons of the lateral geniculate nucleus operate in two distinct modes: "relay" mode and "burst" mode. Relay mode occurs primarily in the alert state, and synaptic transmission through this nucleus is highly effective. In contrast, burst mode has been primarily associated with inattention, drowsiness, and sleep, and synaptic transmission through the thalamus is depressed. Considerable effort has gone into understanding the mechanisms underlying these thalamic modes and their role in visual perception, and thalamic bursts have been linked to mechanisms of attention. However, a crucial link in our understanding of the perceptual consequences of thalamic bursting has remained unexplored: we do not know the fate of bursting thalamic impulses at the geniculocortical synapse. Our preliminary work in the somatosensory system has shown a potent enhancement in the synaptic impact of thalamocortical bursts onto a class of cortical inhibitory neuron. This result, if applicable to the geniculocortical visual system, would impact current thinking on the role of geniculocortical bursts in visual processing. The proposed experiments will extend these results to the visual thalamocortical system and will (1) examine the synaptic impact of both visually elicited and "spontaneous" bursting geniculocortical impulses on excitatory and inhibitory visual cortical populations of layer 4, and (2) examine the intracortical spread of excitation that results from both spontaneous and visually elicited geniculocortical bursts. All experiments will be performed in awake subjects using novel extracellular and intracellular multi-electrode methods. The activity of geniculocortical projection neurons and visual cortical neurons of different classes within visual cortex will be simultaneously studied, and interactions among these identified neurons will be analyzed using methods of cross-correlation and spike-triggered averaging of post-synaptic potentials. We hypothesize that bursting geniculocortical impulses generate an enhanced activation and spread of excitation within the visual cortical network. These data will offer a unique view of visual processing by geniculocortical networks studied under natural conditions in the awake state.